title: Emerging 8-methoxyfluoroquinolone resistance among methicillin-susceptible Staphylococcus epidermidis isolates recovered from patients with endophthalmitis.
abstract: Fluoroquinolones remain the most commonly used antimicrobials for the prevention and management of bacterial endophthalmitis. Coagulase-negative staphylococci are the most frequently recovered pathogens. Increasing resistance among this group has paralleled the presence of methicillin resistance. From 2005 to 2010, we recovered 38 methicillin-susceptible Staphylococcus epidermidis (MSSE) isolates from endophthalmitis patients at our institute, including 15 (39.5%) isolates resistant to gatifloxacin and moxifloxacin, members of the C-8-methoxyfluoroquinolones family. Mutations in the quinolone resistance-determining regions (QRDR) of gyrA and parC were determined and correlated with fluoroquinolone MICs based on Etests of these 15 MSSE isolates. High-level resistance (MIC, >32 μg/ml) to gatifloxacin and moxifloxacin was documented for 46.7% of the MSSE isolates, and low-level resistance (MIC, 2 to 4 μg/ml) was determined for 53.3%. The MICs for ciprofloxacin, levofloxacin, and ofloxacin were >32 μg/ml for all isolates. The amino acid substitution Ser84Phe in gyrA was found among all isolates. A second mutation in gyrA (Glu88Lys) resulted in high-level resistance to moxifloxacin and gatifloxacin. Almost all (92.8%) isolates presented double point mutations in the parC gene at codons 80 and 84 with different combinations. Eighty-seven percent of the patients had prior exposure to topical 8-methoxyfluoroquinolones. Prior exposure to the 8-methoxyfluoroquinolones may contribute to the selection of MSSE strains containing multiple mutations in the QRDRs of gyrA and parC that results in low- and high-level resistance to these agents.
authors.affiliation: Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors.forename: Paulo J M
authors.initials: PJ
authors.lastname: Bispo
authors.forename: Eduardo C
authors.initials: EC
authors.lastname: Alfonso
authors.forename: Harry W
authors.initials: HW
authors.lastname: Flynn
authors.forename: Darlene
authors.initials: D
authors.lastname: Miller
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D027081:DNA Gyrase / Q000235:genetics; D027101:DNA Topoisomerase IV / Q000235:genetics; D024881:Drug Resistance, Bacterial; D009877:Endophthalmitis / Q000382:microbiology*; D005260:Female; D024841:Fluoroquinolones / Q000494:pharmacology*; D005838:Genotype; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D020125:Mutation, Missense; D013203:Staphylococcal Infections / Q000382:microbiology*; D013212:Staphylococcus epidermidis / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification*
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase